Identification of recent alcohol consumption is a critical component of clinical trials and treatment programs that focus on alcohol use disorders. Unlike other substance abuse treatment programs, wherein urine drug screening provides objective evidence of recent drug use with a window of several days, alcohol focused programs must usually depend on self reports for this information. Ethyl glucuronide (EtG), and ethyl sulfate (EtS), minor metabolites of ethanol, are highly specific and sensitive indicators of recent alcohol ingestion, and can be measured in biological fluids for considerably longer than ethanol itself. Thus, they have promise as much needed objective markers for monitoring recent ethanol use or conversely, documenting abstinence in therapeutic trials and treatment programs. Their application in the therapeutic setting, in contrast to the forensic or epidemiological, has not yet been sufficiently investigated in the context of controlled, well documented clinical trials. We will conduct an ethanol challenge study and investigate EtG/EtS in the context of two NIAAA funded outpatient clinical trials in order to meet the following Specific Aims: AIM 1: We will characterize urinary EtG and EtS elimination, including inter-subject and intrasubject variability and dose dependency following a range of ethanol doses selected to produce blood alcohol concentrations that would be expected following light to heavy drinking. AIM 2: We will determine concentrations and changes in concentration of EtG and EtS at defined intervals in subjects participating in a clinical trial that has a goal of abstinence and AIM 3: in a separate clinical trial that has a goal of moderation. In both, we will correlate these measures with more traditional outcome measures, including self reports, blood alcohol concentrations, carbohydrate deficient transferrin and gamma glutamyl transferase. These studies should provide guidelines for optimal use of these promising new markers in the study and management of alcohol use disorders. PUBLIC HEALTH RELEVANCE: An objective marker and measure of recent alcohol consumption is needed for the optimal investigation of treatment options and for the management of patients in clinical trials and treatment programs respectively. Our proposed studies should define the utility of measuring the minor ethanol metabolites, ethyl glucuronide and ethyl sulfate, in conjunction with the study of new treatments, and also yield guidelines for appropriate use of these markers in the treatment of alcohol use disorders.